Table 2.
Genetic impact of TM6SF2 E167K polymorphism on hepatic histological features in the selected studies.
| First author, publication year, study, [Reference Values for Arterial Stiffness, #2467] | Subgroup | Histological feature | Scoring system [Reference Values for Arterial Stiffness, #2467] | Numbera: (N) | Comparisonb | Statistics | OR(95% CI) | P-value | Adjustment |
|---|---|---|---|---|---|---|---|---|---|
| N. Coppola, 201519 | None | Steatosis | NAS24 | S0/S1/S2/S3: EE:45/69/6/10 EK + KK:2/10/2/4 | S2 + S3 vs. S0 + S1 | Chi-square | 3.56 (1.17–10.8) | 0.02 | None |
| None | Fibrosis | Ishak25 | F0/F1/F2/F3/F4/F5/F6: EE:3/40/35/29/14/7/2 EK + KK:2/5/3/3/3/1/1 | F4-F6 vs. F0-F3 | Chi-square | 1.79 (0.58–5.51) | 0.31 | None | |
| M. Milano, 2015, Milan cohort20 | None | Steatosis | Ishak25 | S0/S1/S2/S3: EE:240/383/87/36 EK + KK:15/36/11/7 | S2 + S3 vs. S0 + S1 | Chi-square | 1.79 (1.01–3.16) | 0.04 | None |
| Genotype3 CHC | Steatosis | Ishak25 | NA | S(X + 1) vs. S(X)c | Ordinal regression | 1.23 (0.60–2.52) | 0.58 | Age, gender, BMI, HCV G3,diabetes, alcohol intake, PNPLA3 I148M | |
| Genotype (1 + 2 + 4) CHC | Steatosis | Ishak25 | NA | S(X + 1) vs. S(X) | Ordinal regression | 1.33 (1.03–1.72) | 0.03 | Age, gender, BMI, diabetes, alcohol intake, PNPLA3 I148M | |
| None | Inflamma tion | Ishak25 | G0-G2/G3-G4/G5-G6/ G7-G8/G9-G10/G11-G12 /G13-G18: EE:26/105/262/209/92/ 39/13 EK + KK: 0/17/26/13/5/4/4 | G(X + 1) vs. G(X)d | Ordinal regression | 1.27 (1.02–2.59) | 0.04 | Age, gender, BMI, HCV G3, diabetes, alcohol intake, ancestry, PNPLA3 I148M | |
| None | Fibrosis | Ishak25 | F0/F1/F2/F3/F4/F5/F6: EE:12/118/201/154/71/60/130 | F6 vs. F1-F5 | Logistic regression | 2.19 (1.18–3.39) | 0.01 | Age, gender, BMI, HCV G3, diabetes, alcohol intake, ancestry, PNPLA3 I148M | |
| None | Fibrosis | Ishak25 | EK + KK: 0/9/18/10/9/2/21 | F(X + 1) vs. F(X)e | Ordinal regression | 1.23 (0.99–1.53) | 0.06 | Age, gender, BMI, HCV G3, diabetes, alcohol intake, ancestry, PNPLA3 I148M | |
| M. Milano, 2015, validation cohort20 | None | Fibrosis | METAVIR27 | NA | F2-F4 vs. F0-F1 | Logistic regression | 1.81 (1.02–3.04) | 0.02 | Age and gender |
| S. Petta, 201522 | None | Steatosis | NAS24 | S0/S1/S2: EE:356/187/107 EK + KK:21/14/9 | S(X + 1) vs. S(X) | Ordinal regression | 1.48 (0.82–2.69) | 0.19 | Age, gender, BMI, HOMA-IR |
| None | Inflamma tion | Scheuer26 | G4/G0 + G1 + G2 + G3: EE: 285/365 EK + KK: 17/27 | G4 vs. G0-G3 | Chi-square | 0.81 (0.43–1.51) | 0.50 | None | |
| None | Fibrosis | Scheuer26 | F0-F2/F3-F4: EE:449/201 EK + KK:33/11 | F3-F4 vs. F0-F2 | Logistic regression | 0.75 (0.34–1.63) | 0.47 | Age, gender, BMI, HOMA-IR, PNPLA3 I148M, and IL-28B rs12979860 | |
| M. Eslam, 201621 | None | Steatosis | NAS24 | S0/S1/S2/S3 EE:922/533/237/86 EK:100/94/22/19 KK:2/4/3/1 | S2 + S3 vs. S0 + S1 | Logistic regression | 1.14 (1.02–1.27) | 0.01 | Age, gender, BMI, HOMA-IR, HCV genotype, alcohol intake, and PNPLA3 I148M |
| Genotype3 CHC | Steatosis | NAS24 | NA | S(X + 1) vs. S(X) | Ordinal regression | 1.05 (0.99–1.08) | 0.50 | Age, gender, BMI, HOMA-IR, and PNPLA3 I148M | |
| Genotype (1 + 2 + 4) CHC | Steatosis | NAS24 | NA | S(X + 1) vs. S(X) | Ordinal regression | 1.12 (1.11–1.13) | 0.04 | Age, gender, BMI, HOMA-IR, and PNPLA3 I148M | |
| None | Inflamma tion | METAVIR27 | G0/G1/G2/G3 EE:75/889/620/194 EK:11/129/74/21 KK:1/1/6/2 | G(X + 1) vs. G(X) | Ordinal regression | 1.04 (0.85–1.26) | 0.10 | Age, gender, steatosis, HOMA-IR, BMI, HCV genotype,alcohol intake, and PNPLA3 I148M | |
| None | Fibrosis | METAVIR27 | F0/F1/F2/F3/F4 EE:232/630/512/248 /156 EK:36/87/60/22/30 KK:1/3/0/5/1 | F2-F4 vs. F0-F1 | Logistic regression | 1.39 (1.04–1.87) | 0.02 | Age, gender, steatosis, HOMA-IR, BMI, HCV genotype, alcohol intake, and PNPLA3 I148M | |
| F4 vs. F0-F3 | Logistic regression | 1.82 (1.01–3.28) | 0.01 | Age, gender, steatosis, HOMA-IR, BMI, HCV genotype, alcohol intake, and PNPLA3 I148M | |||||
| F(X + 1) vs. F(X) | Ordinal regression | 1.07 (1.01–1.14) | 0.04 | Age, gender, steatosis, HOMA-IR, BMI, HCV genotype, alcohol intake, and PNPLA3 I148M |
aS, G and F respectively represent the histological severity on steatosis, inflammation and fibrosis; b TM6SF2 E167K variant is coded in dominant genetic model (EE/EK + KK) for each comparison; cS(X + 1) vs.S(X) means the continuous comparison between subgroups with adjacent advanced and mild steatosis; dG(X + 1) vs.G(X) means the continuous comparison between subgroups with adjacent advanced and mild inflammation; eF(X + 1) vs.F(X) means the continuous comparison between subgroups with adjacent advanced and mild fibrosis.